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The role of thrombi...
The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets
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- Nylander, Martina (författare)
- Linköpings universitet,Farmakologi,Hälsouniversitetet
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- Osman, Abdimajid (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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- Ramström, Sofia, 1973- (författare)
- Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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- Aklint, Emma (författare)
- Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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- Larsson, Anders, 1977- (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Biokemisk struktur och funktion,Department of Medical Sciences, University Hospital, Uppsala, Sweden
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- Lindahl, Tomas (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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(creator_code:org_t)
- Elsevier, 2012
- 2012
- Engelska.
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Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 129:4, s. E51-E58
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Introduction: Arterial thrombi contain more platelets than venous thrombi and are more resistant to fibrinolysis. This resistance could partly be due to plasminogen activator inhibitor 1 (PAI-1) secreted by platelets. The aim of this study was to elucidate differences between thrombin receptors protease-activated receptor (PAR) 1 and 4 and platelet storage, secretion and synthesis of platelet PAI-1, as compared to other platelet alpha-granule proteins such as VEGF and endostatin.Materials and methods: Human isolated platelets were incubated with thrombin (0.5 U/ml), PAR1-activating peptide (AP) (0.4-30 mu M) or PAR4-AP (1.5-300 mu M) for up to 24 hours. ELISA, western blot and fluorescence microscopy were used to measure secretion, contents and localization of PAI-1, VEGF and endostatin. Results: Our results show that PAI-1 and VEGF might be co-localized and that endostatin does not co-localize with either PAI-1 or VEGF. PAI-1 and VEGF show a similar secretion pattern, being more sensitive to low grade PAR1 activation, but secretion was also observed with higher concentrations of PAR4-APs. PAI-1 is secreted in an active form. PAI-1 mRNA was found in platelets, and elevated levels of PAI-1 were detected after 24 hours incubation of platelets.Conclusions: PAI-1 and VEGF, but not endostatin, might be stored in the same alpha-granule in human platelets. PAI-1 and VEGF also show a similar secretion pattern, being more sensitive to PAR1 than to PAR4 activation, but the secretion is not exclusively selective. Our results also show that platelet PAI-1 is increased if incubated for 24 hours, both with addition of PAR1-activating peptide and without activation, which could indicate de novo synthesis.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Nyckelord
- Blood Platelets
- PAR1
- PAR4
- Plasminogen Activator Inhibitor 1
- Thrombin
- VEGF
- MEDICINE
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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